title: Elastin binding protein and FKBP65 modulate in vitro self-assembly of human tropoelastin.
abstract: Elastin is a protein that provides the unusual properties of extensibility and elastic recoil to tissues. Assembly of polymeric elastin into its final architecture in the extracellular matrix involves both self-aggregation properties of its monomeric precursor, tropoelastin, and interactions with several matrix-associated proteins that appear to act by modulating the intrinsic self-assembly of tropoelastin. Because of its highly nonpolar character and propensity to self-aggregate, it has been suggested that mechanisms limiting self-aggregation must also be present during the transit of tropoelastin through the cell prior to secretion. Both the elastin binding protein (EBP) and FKBP65 have been suggested to fulfill that role in the Golgi and endoplasmic reticulum compartments of the cell, respectively. However, details about the nature of the interactions between these proteins as well as about the mechanism by which they may act to limit self-aggregation are lacking. In this study, we demonstrate that both EBP and FKBP65 have strong binding affinities for tropoelastin, with the dissociation constant of EBP approximately 4-fold lower than that of FKBP65. Both proteins also modify the kinetics of self-assembly of tropoelastin in an in vitro system, consistent with a role in attenuating the premature intracellular self-aggregation of tropoelastin through a mechanism that limits the growth and maturation of aggregates. The ability of FKBP65 to modulate the self-assembly of tropoelastin is independent of its enzymatic activity to promote the cis-trans isomerization of proline residues in proteins.
authors.affiliation: Research Institute, The Hospital for Sick Children , Toronto, ON M5G 1X8, Canada.
authors.forename: Ming
authors.initials: M
authors.lastname: Miao
authors.forename: Sean E
authors.initials: SE
authors.lastname: Reichheld
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Muiznieks
authors.forename: Yayi
authors.initials: Y
authors.lastname: Huang
authors.forename: Fred W
authors.initials: FW
authors.lastname: Keeley
mesh_terms: D004549:Elastin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D055503:Protein Multimerization; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014333:Tropoelastin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D011956:Receptors, Cell Surface; D014333:Tropoelastin; C054901:elastin-binding proteins; D004549:Elastin; D022021:Tacrolimus Binding Proteins; C110054:FKBP10 protein, human